The rat is a widely used animal model for biological investigation including
many pharmacological, neurobiological and physiological studies. Over the last
few years there has been a significant increase in the amount of information
available on the rat genome and genetics. We have therefore begun to develop
the tools to allow us to exploit this new information resource in order to perform
large-scale expression studies of rat systems. We have developed a cDNA sequence-based
database named RATACE, based on the widely used platform of ACeDB. It
currently contains all the publicly available rat sequence, with the exception
of ESTs. Sequence comparison has allowed sequences originating from the
same gene to be identified and clustered, and sequence alignments can be viewed
graphically from within the database. We are currently developing it as
a tool for handling all the reagents and data required for, and generated by,
large-scale expression studies. Expression studies are being carried out
using RT-PCR and high-density microarrays. To date, we have over 1,000
working primer pairs for rat genes and have used these to profile the expression
of each gene over a range of 22 rat tissues using RT-PCR. We have also
been optimising the conditions necessary for spotting these PCR products on
glass slides to act as probes for microarrays, as well as determining how they
perform during hybridisation. We are currently scaling up the production
of probes for the rat microarrays. It is our intention to use these tools
on rat pharmacological models to further our understanding of the mechanism
of drug action, as well as to identify novel therapeutic targets.